crossing96/oncoscreening huggingface dataset:
BCG Intolerance in Nonmuscle Invasive Bladder Cancer-A Systematic Review.	BACKGROUND: Most patients with localized bladder cancer are initially managed with endoscopic resection. For high-grade nonmuscle invasive bladder cancer (NMIBC), intravesical Bacillus Calmette-Guerin (BCG) therapy is the gold standard adjuvant treatment. However, 30%-40% of patients fail BCG treatment with lack of response or disease relapse. An understudied area of treatment failure is BCG intolerance, where patients drop out of treatment due to adverse effects. OBJECTIVES: To examine the incidence and underlying reasons for BCG intolerance among adult patients with NMIBC. METHODS: We conducted a search on Embase, MEDLINE, and Cochrane Central Register of Controlled Trials for studies from January 1, 1974 to January 10, 2023, retrieving 3340 articles. Two authors independently conducted screening and data extraction with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Inclusion criteria include English-language studies reporting dropout rates and reasons for discontinuation of BCG therapy in NMIBC patients. RESULTS: BCG dropout rates reported among the 28 included studies varied widely from 0% to 52% (estimated summary proportion 12.8%, 95% CI 9%-17%). There was significant heterogeneity in study design. Subgroup analyses show a dose-dependent effect on dropout rates (3.3% vs. 20%, X(2) = 83.6, p = < 2.2 × 10(-16)). Dropout rates vary with BCG strains: the Connaught strain had the highest at 21.1%, while the Pasteur strain had 2%. Clinical outcomes for BCG intolerance are not widely reported. CONCLUSIONS: Dropout rates due to BCG intolerance average 12.8%. As cessation of treatment could lead to an increased risk in progression or recurrence of disease, strategies to mitigate BCG intolerance would be valuable.	bladder
Microbial Product Cocktails for Personalized Cancer Immunotherapy.	The human immune system has evolved to interact with various commensal and pathogenic bacteria in intricate and nuanced ways. While the diversity of bacteria presents fundamental challenges in understanding immune-microbe interactions, it also offers ample opportunities for developing effective immunomodulatory therapies. Here we show microbial product cocktails as an alternative class of immunotherapy for cancer. Using freshly resected tumors from bladder cancer patients, an immuno-comparative analysis of recruitment and enhancement assay, and an artificial intelligence-guided optimization workflow, we establish a personalized platform for identifying potent microbial product cocktails that promote recruitment, infiltration, and activation of immune cells for cancer treatment. In an orthotopic mouse bladder cancer model, microbial product cocktails demonstrate immunoenhancement and improve survival rates compared with standard bacillus Calmette-Guérin immunotherapy.	bladder
Final clinical analysis of pre-operative ipilimumab and nivolumab in locally advanced urothelial cancer and exploration of tumor-draining lymph node composition: The NABUCCO trial.	BACKGROUND: Pre-operative immune checkpoint blockade (ICB) with ipilimumab and nivolumab has shown encouraging pathological complete response (pCR) rates in stage III urothelial cancer (UC). A previous analysis of NABUCCO suggested that ipilimumab 3 mg/kg is more effective than ipilimumab 1 mg/kg. However, long-term progression-free and overall survival (PFS, OS) following pre-operative combination ICB are unknown. METHODS: In NABUCCO, 54 patients received pre-operative ipilimumab plus nivolumab in different dosing regimens. PFS and OS were determined for the entire NABUCCO population and various clinically relevant subgroups. We explored ICB effects on the cellular composition of tumor-draining lymph nodes (tdLN) from ICB-treated patients (n = 5) and untreated or chemotherapy-treated patients (n = 5) using multiplex immunofluorescence for the PhenoCycler Fusion (Akoya). RESULTS: With a median follow-up of 70 months, PFS and OS at 60 months were 67 % and 70 %, respectively, for the entire study. PFS and OS at 60 months were similar for patients with residual non-muscle invasive UC (NMIBC) and patients with a pCR. The presence of a nodal micrometastasis (<2 mm) after ICB, the development of grade ≥ 3 immune-related adverse events (irAE) and corticosteroids or antibiotics did not negatively impact survival. We observed smaller distances from CD20(+) cells to CD14(+) cells in tdLN following ICB compared to tdLN from untreated or chemotherapy-treated patients. CONCLUSIONS: Our data demonstrate a 5-year PFS of 67 % and OS of 70 % after pre-operative ICB in stage III UC. Survival was not impaired for patients with residual NMIBC, a nodal micrometastasis at resection, grade ≥ 3 irAE or corticosteroid use. CLINICAL TRIAL REGISTRATION NUMBER: NCT03387761.	bladder
A Rare Case of Primary Bladder Lymphoepithelial Carcinoma.	BACKGROUND: Bladder cancer is a common malignant tumor of the urinary system. Although lymphoepithelial carcinoma can occur in the liver, breast, thymus, lungs, skin, and other organs, its presence in the urinary system is exceptionally rare. METHODS: We report the case of a 50-year-old man who presented to our hospital with hematuria. Urinary tract computed tomography revealed a malignant bladder tumor, with an enhancing nodule measuring 9 mm in the posterior wall of the bladder. The patient received transurethral resection of the bladder tumor, followed by arterial embolization chemotherapy and intravenous chemotherapy combined with immunotherapy successively, and finally underwent cystoscopy follow-up to monitor the condition. RESULTS: After transurethral resection of the bladder tumor, immunohistochemistry revealed tumor cells appearing as syncytial bodies with unclear boundaries. The nuclei were large and vacuolated, with marked infiltration of lymphoplasmacytes observed both between and within the tumor islands. The markers were as follows: cytokeratin 7 (CK7) (+), CK20 (-), S-100 (-), prostate-specific antigen (PSA) (-), Desmin (-), Melanoma (-), Epstein-Barr virus-encoded RNA (EBER) (-), spalt like transcription factor 4 (SALL4) (-), P63 (-), CKpan (+), GATA binding protein 3 (GATA-3) (-), epithelial membrane antigen (EMA) (+), P40 (-), cluster of differentiation (CD)117 (+), CD20 (-), CD3 (-), CD30 (-), placental alkaline phosphatase (PLAP) (-), CD15 (small weak+), and Ki67 (35%+). The patient was diagnosed with lymphoepithelial carcinoma. CONCLUSIONS: The patient remained recurrence-free at 11 months of follow-up after gemcitabine bladder infusion chemotherapy, arterial drug-infusion embolization, systemic chemotherapy, and immunotherapy.	bladder
Targeting GRB2-Akt-SREBP1 signaling axis by saponins from Paris polyphylla Smith var. yunnanensis (Franch.) Hand.-Mazz to overcome cisplatin resistance in bladder cancer.	"ETHNOPHARMACOLOGICAL RELEVANCE: Paris polyphylla Smith var. yunnanensis (Franch.) Hand.-Mazz., known as ""Chonglou"" in traditional Chinese medicine, is clinically used in cancer therapy, with saponins identified as the key antitumor constituents. However, the therapeutic potential and mechanisms of the total saponins from P. polyphylla var. yunnanensis (PPT) against bladder cancer, particularly their ability to overcome chemoresistance, remain unexplored. AIM OF THE STUDY: This study aimed to investigate PPT's anti-bladder cancer effects and mechanisms, with a focus on its potential to overcome cisplatin resistance. MATERIALS AND METHODS: We established a UPLC-DAD method for saponin profiling and developed an eco-friendly extraction protocol using hydroxypropyl-β-cyclodextrin-assisted extraction combined with macroporous resin purification to prepare PPT. Anti-cancer efficacy was assessed in bladder cancer cell lines, mouse/zebrafish xenograft models, and cisplatin-resistant models. Mechanistic investigations integrated network pharmacology, metabolomics, molecular docking, and experimental validations (siRNA silencing, western blotting, flow cytometry, molecular dynamics simulations, cellular thermal shift assay, and surface plasmon resonance). RESULTS: The hydroxypropyl-β-cyclodextrin-based extraction system enhanced PPT purity by 15-fold, with the purified fraction showing dose-dependent anti-bladder cancer activity in vitro and in vivo. Mechanistically, PPT exerted anti-proliferative, pro-apoptotic, anti-lipogenic, and chemosensitizing effects by inhibiting the growth factor receptor binding protein 2 (GRB2)-mediated Akt-SREBP1 signaling axis. Notably, polyphyllin VII, a key constituent of PPT, was identified as a novel GRB2 inhibitor, potently suppressing bladder cancer progression and overcoming cisplatin resistance. CONCLUSION: This study demonstrates that targeting the GRB2-Akt-SREBP1 signaling axis is a promising strategy for bladder cancer therapy, further establishing PPT as a multicomponent phytomedicine and PPVII as a novel GRB2 inhibitor with high translational potential."	bladder
Bridging Perspectives: Integrating urologist and cytopathologist insights of urine cytology.	In this comprehensive review, we explore the integration of both cytopathologic and urologic perspectives around interpretation of urine cytology under the Paris System for Reporting Urinary Cytology (TPS) and clinical management. Urine cytology is a pivotal diagnostic tool for urologists, especially in the detection and management of high-grade urothelial carcinoma (HGUC). The review highlights how TPS has standardized urine cytology interpretations through consistent diagnostic criteria and reduced atypical diagnoses. This standardization aids in communication between pathologists and clinicians. There is an educational need to foster more effective collaboration between urologists and cytopathologists. Clinicians are not formally educated about TPS, and guidelines do not exist for how TPS diagnostic categories should impact patient treatment/management. Therefore, as TPS continues to evolve, it is important for pathologists to understand how urologists perceive TPS and use its diagnostic categories. This review addresses the clinical management of various diagnostic categories under TPS, illustrating how urologists integrate urine cytology results with endoscopic and radiologic data to monitor recurrence, progression, and metastasis of bladder cancer. It also covers the adjunctive use of urinary biomarkers and advanced cystoscopic techniques to enhance diagnostic accuracy. By bridging cytopathologic insights with urologic clinical applications, this review provides a holistic understanding of the diagnostic and management strategies for bladder cancer, underscoring the indispensable role of urine cytology in urologic practice.	bladder
Development and Validation of a Preoperative MRI Habitat Radiomics Model to Predict Variant Histology in Bladder Cancer.	BACKGROUND: Bladder cancer (BCa) with variant histology (VH) is aggressive, leading to poor prognosis and resistance to neoadjuvant treatment (NAT). Preoperative identification of VH may be important for informing treatment options. PURPOSE: To develop and validate a multiparametric MRI-based ensemble model to identify VH in BCa and explore its association with disease-free survival (DFS) and NAT response. STUDY TYPE: Retrospective. SUBJECTS: Six hundred twenty patients with pathologically confirmed BCa (median age, 65 years [IQR: 56, 73], 145 female) from four centers who underwent preoperative MRI, were divided into a training (n = 311), internal validation (n = 54) from Center 1, and three external validation datasets (n = 85, 68, and 102, respectively). Two additional cohorts, DFS (n = 75) and NAT (n = 69) cohorts, were collected from Center 1 to evaluate prognosis. FIELD STRENGTH/SEQUENCE: 3T, non-fat suppressed T2-weighted imaging using fast spin echo, diffusion-weighted imaging using single-shot echo planar imaging, and T1-weighted dynamic contrast-enhanced sequence using 3D gradient echo sequence. ASSESSMENT: Habitat, radiomic, clinical, clinical-radiomic based, and the VHRisk Score (VHRiS) models were constructed for evaluating VH. The prognostic value of VHRiS for DFS and pathological complete response (pCR) rate was further evaluated. STATISTICAL TESTS: Mann-Whitney U test, t-test, ROC analysis (AUC), Kaplan-Meier curves, log-rank test, and SHapley Additive exPlanations (SHAP) analysis. RESULTS: The VHRiS model demonstrated favorable accuracy (AUCs: training, 0.971; internal validation, 0.895; external validation, 0.898-0.974). Low-risk patients (VHRiS ≥ 0.863) exhibited significantly longer DFS than high-risk patients (4.20 months vs. 3.08 months) in the DFS cohort (median follow-up period: 13.19 months [IQR: 6.54, 31.91]). They also showed a higher pCR rate than high-risk patients (64% vs. 33%) in the NAT cohort. DATA CONCLUSIONS: The VHRiS model may be a robust tool for identifying VH, and may offer a potential method for risk stratification and prognosis prediction in patients with BCa. LEVELS OF EVIDENCE: 4. TECHNICAL EFFICACY STAGE: 2.	bladder
The Paris system for reporting urinary cytology: what worked and what still needs to be improved.	Urine cytology has long been a challenging diagnostic modality due to its low sensitivity for low-grade urothelial neoplasms and high interobserver variability. The introduction of The Paris System (TPS) in 2016 marked a pivotal shift towards standardisation, with a primary focus on detecting high-grade urothelial carcinoma (HGUC). This review evaluates the impact of TPS on diagnostic accuracy, reproducibility, and clinical utility. It also highlights the system's limitations, including issues with nuclear-to-cytoplasmic (N/C) ratio estimation, cellular degeneration, and the underrepresentation of HGUC variants. The second edition of TPS (TPS 2.0) addresses many of these concerns, offering refined criteria and visual aids. However, further improvements are needed, particularly in the integration of molecular diagnostics and artificial intelligence.	bladder
First-line treatment options for metastatic urothelial carcinoma: balancing efficacy, safety, and individual values and preferences through shared decision making.	Metastatic urothelial carcinoma (mUC) remains a disease with poor prognosis. While conventional platinum-based chemotherapy has long served as the standard first-line treatment, its survival benefit is limited, particularly in cisplatin-ineligible patients. The introduction of immune checkpoint inhibitors and antibody-drug conjugates as part of sequential treatment has improved outcomes, with pembrolizumab, avelumab, and enfortumab vedotin (EV) providing survival benefit in later lines. In 2024, the EV plus pembrolizumab (EV + P) regimen demonstrated a striking improvement in overall survival compared to chemotherapy followed by maintenance avelumab, representing a paradigm shift toward maximizing efficacy at the initial treatment stage. However, the safety profile of EV + P has specific safety concerns, including skin reactions, peripheral neuropathy, and immune-related adverse events. To fully realize the survival benefits of this combination, careful management and continued treatment are essential, especially in older adults, patients with poor general condition, or those with limited family support. In real-world practice, treatment decisions should be based not only on efficacy but also on safety, patient values and preferences, general condition, and social background. Therefore, shared decision making (SDM) has become increasingly important as a practical approach to adjust first-line treatment strategies. This review summarizes the developing landscape of first-line treatment options for mUC, evaluates the clinical and real-world implications of EV + P, and highlights the importance of SDM in balancing efficacy, safety, and personal values in routine clinical care.	bladder
French recommendations of the AFU Oncology Committee for Bladder Cancer: Update 2025.	"PURPOSE OF THIS DOCUMENT: The Oncology Committee of the French Urology Association (CCAFU) is proposing a 2025 summary of recommendations' changes for the management of bladder cancer (BCa). METHODS: A systematic review of the literature from July 2024 to September 2025 was conducted by the CCAFU on the evolutions of diagnostic and therapeutic management of BCa evaluating the newly published references with their level of evidence. RESULTS: On NMIBC BCa guidelines: the addition of a new recommendation to the sections ""4.3. High-risk tumours"" and ""5.2. BCG-endovesical therapy"" related to the association BCG + systemic immunotherapy. On MIBC guidelines: new recommendations to the sections ""3.1.1. Neoadjuvant cisplatin-based chemotherapy"" and ""3.2.2. Adjuvant immunotherapy treatment"" related to the perioperative combination of chemotherapy and immunotherapy. CONCLUSION: This 2025 summary of changes of French recommendations should help physicians to stay up-to-date with recent evolutions and aim to improve the management of BCa patients."	bladder
Loss of METTL3 m6A methyltransferase results in short-term progression and poor treatment outcome of bladder cancer patients.	Bladder cancer (BlCa) exhibits a highly heterogeneous molecular landscape and treatment response, underlining the pressing need for personalized prognosis. N6-methyladenosine (m6A) constitutes the most abundant RNA modification, modulates RNA biology/metabolism, and maintains cellular homeostasis, with its dysregulation involved in cancer initiation and progression. Herein, we evaluated the clinical value of METTL3 m6A methyltransferase, the main catalytic component of m6A methylation machinery, in improving BlCa patients' risk stratification and prognosis. The screening cohort of the study included 213 patients. The UROMOL (n = 535) was analyzed as a validation cohort for non-muscle-invasive BlCa (NMIBC), while the TCGA-BLCA (n = 412) and Mariathasan et al. (n = 348) cohorts were analyzed for muscle-invasive BlCa (MIBC). Disease recurrence/progression and patients' mortality were assessed as clinical endpoints for NMIBC and MIBC, respectively. Internal validation of Cox regression models was conducted using bootstrap analysis, while the clinical utility for patient prognosis was evaluated through decision curve analysis. Reduced METTL3 expression was correlated with muscle-invasive disease and tumors of advanced stage. Loss of METTL3 expression at diagnosis was strongly associated with higher risk of short-term progression (HR = 2.903, 95% CI: 1.303-6.464, p = 0.006) to invasive stages in NMIBC and with worse survival of MIBC patients (HR = 1.908, 95% CI: 1.020-3.567, p = 0.042). Consistently, validation cohorts confirmed the poor treatment outcomes in patients exhibiting loss of METTL3. Finally, METTL3-fitted multivariate models improved risk stratification and offered superior clinical benefit for NMIBC and MIBC prognostication compared to clinically established disease markers. Overall, loss of METTL3 expression correlates with inferior treatment outcomes in BlCa, driving more accurate risk stratification and ameliorating patients' prognosis in BlCa.	bladder
Cost-effectiveness of enfortumab vedotin plus pembrolizumab as a first-line treatment of locally advanced or metastatic urothelial carcinoma in the United States.	OBJECTIVE: Enfortumab vedotin plus pembrolizumab (EV+Pem) was recently approved in the United States as the new first-line standard of care for locally advanced or metastatic urothelial carcinoma (la/mUC). We assessed the cost-effectiveness of EV+Pem as first-line treatment for la/mUC from a US third-party payer perspective, using the most recent database lock (data cutoff: 8 August 2024) from the Phase III EV302/KEYNOTE-A39 study (NCT04223856). METHODS: A partitioned survival model assessed the cost-effectiveness of EV+Pem versus gemcitabine and cisplatin/carboplatin followed by maintenance avelumab if not progressed (GP/GC ± Ave) in la/mUC patients. Standard and flexible spline parametric models were fitted to patient-level overall survival (OS) and progression-free survival (PFS) data from EV-302. Treatment discontinuation, utilities, and other clinical inputs were also based on EV-302. Cost inputs were sourced from literature or public databases. A cisplatin-eligible (Cis-E) subpopulation analysis compared EV+Pem versus nivolumab plus gemcitabine and cisplatin (Nivo + GP) and other platinum-based chemotherapies. A network meta-analysis based on the EV-302 and CheckMate-901 studies informed the OS and PFS hazard ratios for Nivo + GP versus EV+Pem. RESULTS: For the overall population, EV+Pem was projected to extend 2.58 life-years (LYs), or 1.76 quality-adjusted life-years (QALYs), versus GP/GC ± Ave, with an incremental cost-effectiveness ratio (ICER) of $180,631/QALY. Probabilistic sensitivity analyses (PSA) showed that EV+Pem had a 77% probability of being more cost-effective versus GP/GC ± Ave at a willingness-to-pay (WTP) threshold of $200,000/QALY. For the Cis-E subpopulation, EV+Pem was projected to extend 2.37 LYs (1.45 QALYs) versus Nivo + GP, with an ICER of $136,475/QALY. The PSA showed that EV+Pem had a 59% probability of being most cost-effective among all the treatment regimens considered, including platinum-based chemotherapies, at a WTP threshold of $200,000/QALY. CONCLUSIONS: EV+Pem is cost-effective compared to platinum-based regimens for the treatment of previously untreated la/mUC from a US third party payer perspective at a willingness-to-pay threshold of $200,000/QALY.	bladder
Revolutionizing bladder cancer research: Harnessing 3D organoid technology to decode tumor heterogeneity and propel personalized therapeutics.	Bladder cancer (BC), characterized by remarkable tumor heterogeneity, remains a challenging malignancy with limited therapeutic options. Emerging three-dimensional (3D) organoid models are transforming our understanding of BC biology by closely mimicking the complex tumor microenvironment (TME) and cellular interactions, far surpassing traditional two-dimensional (2D) cell culture systems. This review underscores the innovative advances in bladder cancer organoid technology, emphasizing their unique strengths in capturing intratumoral heterogeneity, enhancing drug sensitivity assessments, and facilitating personalized treatment approaches. We discuss diverse organoid systems, including spheroids, assembloids, and patient-derived organoid xenografts (PDOX), highlighting their exceptional ability to replicate individual patient tumor profiles. Furthermore, we explore integrated organoid-on-chip cultivation techniques incorporating 3D bioprinting and microfluidics, which notably improve precision, reproducibility, and scalability in organoid-based drug screening platforms. We advocate for optimized organoid cultivation protocols and synergistic integration with high-throughput analytical technologies, aiming ultimately to accelerate regimen breakthroughs in personalized medicine for bladder cancer patients.	bladder